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Stroke is the leading cause of disability worldwide and the second leading cause of death. Large and small strokes and disease of small cerebral blood vessels can lead to dementia, as well as milder degrees of cognitive deficit (vascular cognitive impairment). Strokes may be large or small and may occur with or without bleeding in the brain. The brain can also be damaged by a long-term lack of sufficient blood flow with loss of the axons, needed for neurons to communicate with each other. Attention to the four reserve factors (cognitive, physical, psychological, and social) can help to prevent stroke as well as improve recovery and diminish the effect of stroke on cognitive function. Cerebrovascular disease makes a very important contribution to cognitive impairment with aging. Recent studies have demonstrated several ways in which bacteria that reside in the mouth are involved in causing strokes. There are many modifiable risk factors for stroke including a high-fat diet, obesity, smoking, poor oral hygiene, physical inactivity, atrial fibrillation, alcoholism. Lifestyle factors play a large role in the risk of all forms of stroke
A large proportion of Alzheimer’s disease (AD) patients have coexisting subcortical vascular dementia (SVaD), a condition referred to as mixed dementia (MixD). Brain imaging features of MixD presumably include those of cerebrovascular disease and AD pathology, but are difficult to characterize due to their heterogeneity.
To perform an exploratory analysis of conventional and non-conventional structural magnetic resonance imaging (MRI) abnormalities in MixD and to compare them to those observed in AD and SVaD.
We conducted a cross-sectional, region-of-interest-based analysis of 1) hyperintense white-matter signal abnormalities (WMSA) on T2-FLAIR and hypointense WMSA on T1-weighted MRI; 2) diffusion tensor imaging; 3) quantitative susceptibility mapping; and 4) effective transverse relaxation rate (R2*) in N = 17 participants (AD:5, SVaD:5, MixD:7). General linear model was used to explore group differences in these brain imaging measures.
Model findings suggested imaging characteristics specific to our MixD group, including 1) higher burden of WMSAs on T1-weighted MRI (versus both AD and SVaD); 2) frontal lobar preponderance of WMSAs on both T2-FLAIR and T1-weighted MRI; 3) higher fractional anisotropy values within normal-appear white-matter tissues (versus SVaD, but not AD); and 4) lower R2* values within the T2-FLAIR WMSA areas (versus both AD and SVaD).
These findings suggest a preliminary picture of the location and type of brain imaging characteristics associated with MixD. Future imaging studies may employ region-specific hypotheses to distinguish MixD more rigorously from AD or SVaD.
Cerebrovascular disease is regarded as a potential cause of late-life depression. Yet, evidence for associations of neuroimaging markers of vascular brain disease with depressive symptoms is inconclusive. We examined the associations of neuroimaging markers and depressive symptoms in a large population-based study of middle-aged and elderly persons over time.
A total of 4943 participants (mean age = 64.6 ± 11.1 years, 55.7% women) from the Rotterdam Study were included. At baseline, total brain volume, gray matter volume, white matter volume, white matter hyperintensities volume, cortical infarcts, lacunar infarcts, microbleeds, white matter fractional anisotropy, and mean diffusivity (MD) were measured with a brain MRI (1.5T). Depressive symptoms were assessed twice with the Center for Epidemiologic Studies Depression scale (median follow-up time: 5.5 years, IQR = 0.9). To assess temporal associations of neuroimaging markers and depressive symptoms, linear mixed models were used.
A smaller total brain volume (β = −0.107, 95% CI −0.192 to −0.022), larger white matter hyperintensities volume (β = 0.047, 95% CI 0.010–0.084), presence of cortical infarcts (β = 0.194, 95% CI 0.047–0.341), and higher MD levels (β = 0.060, 95% CI 0.022–0.098) were cross-sectionally associated with more depressive symptoms. Longitudinal analyses showed that small total brain volume (β = −0.091, 95% CI −0.167 to −0.015) and presence of cortical infarcts (β = 0.168, 95% CI 0.022–0.314) were associated with increasing depressive symptoms over time. After stratification on age, effect sizes were more pronounced at older ages.
Neuroimaging markers of white matter microstructural damage were associated with depressive symptoms longitudinally in this study of middle-aged and elderly persons. These associations were more pronounced at older ages, providing evidence for the role of white matter structure in late-life depressive symptomatology.
Neurodegenerative diseases are a pathologically, clinically and genetically diverse group of disorders without effective disease-modifying therapies. Pathologically, these disorders are characterised by disease-specific protein aggregates in neurons and/or glia and referred to as proteinopathies. Many neurodegenerative diseases show pathological overlap with the same abnormally deposited protein occurring in anatomically distinct regions, which give rise to specific patterns of cognitive and motor clinical phenotypes. Sequential distribution patterns of protein inclusions throughout the brain have been described. Rather than occurring in isolation, it is increasingly recognised that combinations of one or more proteinopathies with or without cerebrovascular disease frequently occur in individuals with neurodegenerative diseases. In addition, complex constellations of ageing-related and incidental pathologies associated with tau, TDP-43, Aβ, α-synuclein deposition have been commonly reported in longitudinal ageing studies. This review provides an overview of current classification of neurodegenerative and age-related pathologies and presents the spectrum and complexity of mixed pathologies in community-based, longitudinal ageing studies, in major proteinopathies, and genetic conditions. Mixed pathologies are commonly reported in individuals >65 years with and without cognitive impairment; however, they are increasingly recognised in younger individuals (<65 years). Mixed pathologies are thought to lower the threshold for developing cognitive impairment and dementia. Hereditary neurodegenerative diseases also show a diverse range of mixed pathologies beyond the proteinopathy primarily linked to the genetic abnormality. Cases with mixed pathologies might show a different clinical course, which has prognostic relevance and obvious implications for biomarker and therapy development, and stratifying patients for clinical trials.
Endovascular thrombectomy (EVT) has significantly improved outcomes for patients with acute ischemic stroke due to large vessel occlusion. However, despite advances, more than half of patients remain functionally dependent 3 months after their initial stroke. Anesthetic strategy may influence both the technical success of the procedure and overall outcomes. Conventionally, general anesthesia (GA) has been widely used for neuroendovascular procedures, particularly for the distal intracranial circulation, because the complete absence of movement has been considered imperative for procedural success and to minimize complications. In contrast, in patients with acute stroke undergoing EVT, the optimal anesthetic strategy is controversial. Nonrandomized studies suggest GA negatively affects outcomes while the more recent anesthesia-specific RCTs report improved or unchanged outcomes in patients managed with versus without GA, although these findings cannot be generalized to other EVT capable centers due to a number of limitations. Potential explanations for these contrasting results will be addressed in this review including the effect of different anesthetic strategies on cerebral and systemic hemodynamics, revascularization times, and periprocedural complications.
There is international variability in whether neurological determination of death (NDD) is conceptually defined based on permanent loss of brainstem function or “whole brain death.” Canadian guidelines are not definitive. Patients with infratentorial stroke may meet clinical criteria for NDD despite persistent cerebral blood flow (CBF) and relative absence of supratentorial injury.
We performed a multicenter cohort study involving patients that died from ischemic or hemorrhagic stroke in Alberta intensive care units from 2013 to 2019, focusing on those with infratentorial involvement. Medical records were reviewed to determine the incidence and proportion of patients that met clinical criteria for NDD; whether ancillary testing was performed; and if so, whether this demonstrated the absence of CBF.
There were 95 (27%) deaths from infratentorial and 263 (73%) from supratentorial stroke. Sixteen patients (17%) with infratentorial stroke had neurological examination consistent with NDD (0.55 cases per million per year). Among patients that underwent confirmatory evaluation for NDD with an apnea test, ancillary test (radionuclide scan), or both, ancillary testing was more common with infratentorial compared with supratentorial stroke (10/12 (85%) vs. 25/47 (53%), p = 0.04). Persistent CBF was detected in 6/10 (60%) patients with infratentorial compared with 0/25 with supratentorial stroke (p = 0.0001).
Infratentorial stroke leading to clinical criteria for NDD occurs with an annual incidence of about 0.55 per million. There is variability in clinicians’ use of ancillary testing. Persistent CBF was detected in more than half of patients that underwent radionuclide scans. Canadian consensus is needed to guide clinical practice.
In France, dairy products contribute to dietary saturated fat intake, of which reduced consumption is often recommended for CVD prevention. Epidemiological evidence on the association between dairy consumption and CVD risk remains unclear, suggesting either null or inverse associations. This study aimed to investigate the associations between dairy consumption (overall and specific foods) and CVD risk in a large cohort of French adults. This prospective analysis included participants aged ≥18 years from the NutriNet-Santé cohort (2009–2019). Daily dietary intakes were collected using 24-h dietary records. Total dairy, milk, cheese, yogurts, fermented and reduced-fat dairy intakes were investigated. CVD cases (n 1952) included cerebrovascular disease (n 878 cases) and CHD (n 1219 cases). Multivariable Cox models were performed to investigate associations. This analysis included 104 805 French adults (mean age at baseline 42·8 (sd 14·6) years, mean follow-up 5·5 (sd 3·0) years, i.e. 579 155 person-years). There were no significant associations between dairy intakes and total CVD or CHD risks. However, the consumption of at least 160 g/d of fermented dairy (e.g. cheese and yogurts) was associated with a reduced risk of cerebrovascular diseases compared with intakes below 57 g/d (hazard ratio = 0·81 (95 % CI 0·66, 0·98), Ptrend = 0·01). Despite being a major dietary source of saturated fats, dairy consumption was not associated with CVD or CHD risks in this study. However, fermented dairy was associated with a lower cerebrovascular disease risk. Robust randomised controlled trials are needed to further assess the impact of consuming different dairy foods on CVD risk and potential underlying mechanisms.
Coronavirus disease 2019 (COVID-19) has become a global pandemic. Previous studies showed that comorbidities in patients with COVID-19 are risk factors for adverse outcomes. This study aimed to clarify the association between nervous system diseases and severity or mortality in patients with COVID-19. We performed a systematic literature search of four electronic databases and included studies reporting the prevalence of nervous system diseases in COVID-19 patients with severe and non-severe disease or among survivors and non-survivors. The included studies were pooled into a meta-analysis to calculate the odds ratio (OR) with 95% confidence intervals (95%CI). We included 69 studies involving 17 879 patients. The nervous system diseases were associated with COVID-19 severity (OR = 3.19, 95%CI: 2.37 to 4.30, P < 0.001) and mortality (OR = 3.75, 95%CI: 2.68 to 5.25, P < 0.001). Specifically, compared with the patients without cerebrovascular disease, patients with cerebrovascular disease infected with COVID-19 had a higher risk of severity (OR = 3.10, 95%CI: 2.21 to 4.36, P < 0.001) and mortality (OR = 3.45, 95% CI: 2.46 to 4.84, P < 0.001). Stroke was associated with severe COVID-19 disease (OR = 1.95, 95%CI: 1.11 to 3.42, P = 0.020). No significant differences were found for the prevalence of epilepsy (OR = 1.00, 95%CI: 0.42 to 2.35, P = 0.994) and dementia (OR = 2.39, 95%CI: 0.55 to 10.48, P = 0.247) between non-severe and severe COVID-19 patients. There was no significant association between stroke (OR = 1.79, 95%CI: 0.76 to 4.23, P = 0.185), epilepsy (OR = 2.08, 95%CI: 0.08 to 50.91, P = 0.654) and COVID-19 mortality. In conclusion, nervous system diseases and cerebrovascular disease were associated with severity and mortality of patients with COVID-19. There might be confounding factors that influence the relationship between nervous system diseases and COVID-19 severity as well as mortality.
Previous research has suggested an association between depression and subsequent acute stroke incidence, but few studies have examined any effect modification by sociodemographic factors. In addition, no studies have investigated this association among primary care recipients with hypertension.
We examined the anonymized records of all public general outpatient visits by patients aged 45+ during January 2007–December 2010 in Hong Kong to extract primary care patients with hypertension for analysis. We took the last consultation date as the baseline and followed them up for 4 years (until 2011–2014) to observe any subsequent acute hospitalization due to stroke. Mixed-effects Cox models (random intercept across 74 included clinics) were implemented to examine the association between depression (ICPC diagnosis or anti-depressant prescription) at baseline and the hazard of acute stroke (ICD-9: 430–437.9). Effect modification by age, sex, and recipient status of social security assistance was examined in extended models with respective interaction terms specified.
In total, 396 858 eligible patients were included, with 9099 (2.3%) having depression, and 10 851 (2.7%) eventually hospitalized for stroke. From the adjusted analysis, baseline depression was associated with a 17% increased hazard of acute stroke hospitalization [95% confidence interval (CI) 1.03–1.32]. This association was suggested to be even stronger among men than among women (hazard ratio = 1.29, 95% CI 1.00–1.67).
Depression is more strongly associated with acute stroke incidence among male than female primary care patients with hypertension. More integrated services are warranted to address their needs.
A 24-year-old female patient diagnosed with cyanotic CHD had undergone a correction procedure at the age of eight. She had a normal motor and mental development until the age of 23. Later she had functional and cognitive decline following heart failure. Brain MRI showed enlargement of the cerebral arterial and venous system. The changes of central nervous system vasculature occurring in operated cyanotic CHD are not well known. Thanks to advances in this field, more cyanotic CHD patients reach adulthood nowadays and clinicians need to be familiar with the neurological conditions and potential neuroradiological changes.
The aim of this study was to model the relationships among white matter hyperintensities (WMHs), depressive symptoms, and cognitive function and to examine the mediating effect of depressive symptoms on the relationship between WMHs and cognitive impairment.
We performed structural equation modeling using cross-sectional data from 1158 patients from the Clinical Research for Dementia of South Korea (CREDOS) registry who were diagnosed with mild-to-moderate dementia. Periventricular white matter hyperintensities (PWMHs) and deep white matter hyperintensities (DWMHs) were obtained separately on the protocol of magnetic resonance imaging (MRI). Depression and cognitive function were assessed using the Korean Form of the Geriatric Depression Scale (KGDS) and the Seoul Neuropsychological Screening Battery (SNSB), respectively.
The model that best reflected the relationships among the variables was the model in which DWMHs affected cognitive function directly and indirectly through the depressive symptoms; on the other hand, PWMHs only directly affected cognitive function.
This study presents the mediation model including the developmental pathway from DWMHs to cognitive impairment through depressive symptoms and suggests that the two types of WMHs may affect cognitive impairment through different pathways.
No data exist on the associations of dietary tomato and lycopene consumption with total and cause-specific mortality. Using the National Health and Nutrition Examination Surveys 1999–2010, we evaluted the long-term impact of tomato and lycopene intake on total and cause-specific (CHD and cerebrovascular disease) mortality. We also assessed the changes in cardio-metabolic risk factors according to tomato and lycopene intake. Vital status to 31 December 2011 was ascertained. Cox proportional hazard regression models (followed by propensity score matching) were used to investigate the link between tomato and lycopene consumption total, CHD and cerebrovascular mortality. Among the 23 935 participants included (mean age = 47·6 years, 48·8 % men), 3403 deaths occurred during 76·4 months of follow-up. Tomato intake was inversely associated with total (risk ratio (RR) 0·86, 95 % CI 0·81, 0·92), CHD (RR 0·76, 95 % CI 0·70, 0·85) and cerebrovascular (RR 0·70, 95 % CI 0·62, 0·81) mortality. Similar inverse associations were found between lycopene consumption, total (RR 0·76, 95 % CI 0·72, 0·81), CHD (RR 0·73, 95 % CI 0·65, 0·83) and cerebrovascular (RR 0·71, 95 % CI 0·65, 0·78) mortality; these associations were independent of anthropometric, clinical and nutritional parameters. Age and obesity did not affect the association of tomato and lycopene consumption with total, CHD and cerebrovascular mortality. C-reactive protein significantly moderated the link between lycopene and tomato intake with total, CHD and cerebrovascular mortality. ANCOVA showed that participants with a higher tomato and lycopene consumption had a more cardio-protective profile compared with those with a lower intake. Our results highlighted the favourable effect of tomato and lycopene intake on total and cause-specific mortality as well as on cardio-metabolic risk factors. These findings should be taken into consideration for public health strategies.
To investigate the predictive ability of the previously established global cerebrovascular disease (CeVD) burden scale on long-term clinical outcomes in a longitudinal study of Asian elderly participants across the spectrum of cognitive impairment.
A case-control study was conducted over a 2-year period involving participants with no cognitive impairment, cognitive impairment-no dementia (CIND), and Alzheimer's disease (AD). Annually, cognitive function was assessed with a comprehensive neuropsychological battery and the clinical dementia rating (CDR) scale was used to stage disease severity.
Of 314 participants, 102 had none/very mild CeVD, 31 mild CeVD, 94 moderate CeVD, and 87 severe CeVD at baseline. There was a 1.14 and 1.42 units decline per year on global cognitive z-scores in moderate and severe CeVD groups, respectively, compared to none/very mild CeVD. Moderate-severe CeVD predicted significant functional deterioration at year 2 (HR = 2.0, 95% CI = 1.2–3.4), and conversion to AD (HR = 6.3, 95% CI = 1.7–22.5), independent of medial temporal atrophy.
The global CeVD burden scale predicts poor long-term clinical outcome independent of neurodegenerative markers. Furthermore, CeVD severity affects the rate of cognitive and functional deterioration. Hence, cerebrovascular burden, which is potentially preventable, is a strong prognostic indicator, both at preclinical and clinical stages of AD, independent of neurodegenerative processes.
Prenatal exposure to famine is associated with an increased risk of metabolic and cardiovascular diseases in the offspring at adult age. The aim of this study was to assess whether prenatal exposure to undernutrition increases the risk of stroke. This study was performed in the Dutch famine birth cohort, which consist of 2414 members who were born between 1943 and 1947 in the Netherlands. In a subsample of 1177 individuals, interviews were conducted using standardized questionnaires to obtain information about medical history (which included specific questions regarding stroke) and lifestyle. Information on stroke-related mortality was collected by linking the cohort with Statistics Netherlands. A Cox’s proportional hazard analysis was performed to calculate hazard ratios (HRs) comparing the incidence of non-fatal stroke between participants who were exposed, subdivided into early, mid and late gestation, and unexposed to famine prenatally. Three cohort members died of stroke. Of the 1177 subjects who responded to the questionnaires 49 (4.2%) survived a stroke. Unadjusted and adjusted HRs for the risk of non-fatal stroke did not show a significant difference between the unexposed and exposed subjects: HR 1.23 (95% CI 0.53–2.83), HR 1.23 (95% CI 0.53–2.82), HR 1.12 (95% CI 0.46–2.71) for those exposed in late, mid and early gestation, respectively. We were unable to find evidence for a major effect of prenatal exposure to famine on the risk of stroke in later life, although one should be aware that this study was underpowered and the study population too selected and young to identify smaller risks.